DESCRIPTION: (Applicant's Description) Dr. Chen is well trained in laboratory investigation, with a Ph.D. in immunology and postdoctoral research experience in the molecular biology of hematopoietic growth factor receptors. He has made the transition to a career in translational clinical research leading the pediatric bone marrow transplant program at Johns Hopkins. His career development plan is to obtain formal training in the theory and methods of clinical investigation leading to the M.H.S. degree, while conducting clinical translational research with mentorship from Georgia Vogelsang. M.D., Clinical Director of the Division of Hematologic Malignancies. Steven Goodman, M.D., M.H.S., Ph.D., will serve as co-mentor with expertise in epidemiology, biostatistics, and clinical trial design. Bone marrow transplantation is used to treat poor-prognosis malignancies and to replace defective hematopoietic cells. For children with poor-prognosis solid tumors, the use of peripheral blood stem cells substantially reduces the morbidity of BMT, and presents the opportunity to perform tandem BMTs to improve tumor control. However. many patients with poor-prognosis pediatric solid tumors fail to mobilize stem cells adequately. New hematopoietic growth factors that act on more primitive cells may recruit new populations of hematopoietic cells to augment peripheral blood stem cell collections. The resulting collections may have different properties, including better engraftment potential per cell. The protocol will compare mobilization of CD34+ cells by chemotherapy + G-CSF + SCF vs. chemotherapy + G-CSF, and will test their engraftment potential in a xenotransplantation model in NOD/SCID mice. For patients with nonmalignant diseases, the toxicity of bone marrow transplantation weighs heavily against its possible benefit. Thus, less toxic transplant therapy must be developed. Mixed donor chimerism may suffice to ameliorate some inherited diseases of hematopoietic cells. Non-marrow- ablative transplant regimens can produce mixed chimerism in patients with hematologic malignancies with much less toxicity than traditional bone marrow transplants. Our hypothesis is that a non-marrow-ablative approach can be adapted for patients with inherited disease, but will require an increase in immune suppression to overcome the barrier of an intact immune system. The protocol will use the continual reassessment method to find the minimum dose of fludarabine in the context of 200 cGy TBI to produce mixed chimerism in patients with hemoglobinopathies.